+

WO1998015531A1 - PROCEDE DE PREPARATION DE SELS ACIDES D'ACIDE η-(PIPERIDYL)BUTYRIQUE - Google Patents

PROCEDE DE PREPARATION DE SELS ACIDES D'ACIDE η-(PIPERIDYL)BUTYRIQUE Download PDF

Info

Publication number
WO1998015531A1
WO1998015531A1 PCT/JP1997/003594 JP9703594W WO9815531A1 WO 1998015531 A1 WO1998015531 A1 WO 1998015531A1 JP 9703594 W JP9703594 W JP 9703594W WO 9815531 A1 WO9815531 A1 WO 9815531A1
Authority
WO
WIPO (PCT)
Prior art keywords
acid
butyric acid
pyridyl
catalyst
formula
Prior art date
Application number
PCT/JP1997/003594
Other languages
English (en)
Japanese (ja)
Inventor
Toshito Sakai
Masayo Nagaoka
Ken Kanno
Original Assignee
Koei Chemical Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Koei Chemical Co., Ltd. filed Critical Koei Chemical Co., Ltd.
Priority to JP51738598A priority Critical patent/JP4247415B2/ja
Priority to EP97943149A priority patent/EP0882712B1/fr
Priority to US09/077,316 priority patent/US6197961B1/en
Priority to DE69721239T priority patent/DE69721239T2/de
Priority to CA002239138A priority patent/CA2239138C/fr
Publication of WO1998015531A1 publication Critical patent/WO1998015531A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/55—Acids; Esters

Definitions

  • the present invention uses the formula (2)
  • ⁇ -(Piperidinole) butyric acid acid salt (2) is either ⁇ -(piperidyl) butyric acid released as it is or from acid acid. It is a useful compound used in the body.
  • the y (piperidyl) butyric acid acid salt (2) is obtained by adding hydrogen to the acid salt of y-(2 pyridinole) butyric acid to convert the pyridin ring into a pyridin ring.
  • a method for producing ⁇ -(pyridyl) butyric acid acid salt (2) by hydrogenating mono (2-pyridyl) butyric acid acid salt is to use platinum oxide as a catalyst.
  • There is a known way to use [J Am. Chem. Soc., 69, 2461 (19447)], and the conventional method described above is based on the acid of-(2-pyridinole) butyric acid in the reaction solution. Hydrogen addition Q is carried out under extremely dilute salt concentration of 2%, which is a practical method due to poor vessel efficiency and low productivity. is not.
  • the above conventional method has a problem that a large amount of platinum oxide needs to be used as a catalyst. That is, in the above literature, a large amount of platinum oxide is used as 43% by weight as Pt with respect to the hydrochloride salt of ⁇ - (4-pyridyl) butyric acid.
  • the present invention provides a catalyst capable of efficiently converting a pyridin ring into a peridin ring by adding hydrogen to an acid salt of ⁇ - (piperidyl) butyric acid.
  • Another object of the present invention is to provide a method for producing an acid salt of y_ (piperidyl) butyric acid (2) with high productivity.
  • R represents a hydrogen atom or an alkyl group
  • A represents an acid.
  • the catalyst used is a Rh catalyst, Pd catalyst or Ru catalyst, ⁇ (piperidyl)
  • the butyric acid acid salt (2) can be produced in a relatively short time with good productivity, and surprisingly, if these catalysts are used, the acid salt of butyric acid (1) can be obtained.
  • R 1 and R 2 represent the same or different phenolic phenolic groups, and are represented by the following formula: Ter (5).
  • formula (6) (Wherein, R 1 and R 2 represent the same or different phenolic phenolic groups, and are represented by the following formula: Ter (5).] And the formula (6)
  • N-COOR 2 (wherein, R, R 1 and R 2 are the same as above) represented by 2- (pyridinolethione) malonic acid diester Below, 2 —
  • step (b) The di-estenole-2 (pyridylethyl) malonate (6) produced in step (a) is hydrolyzed and decomposed in an acidic aqueous solution. And decarboxylation process.
  • the ⁇ _ (pyridyl) butyric acid acid salt (1) produced from the step (a) and the step (b) is subjected to hydrogen addition, and the ⁇ (pidinole) butyric acid acid salt (2) is added.
  • V-(pyridyl) butyric acid acid salt (1) certain impurities contained in It has an adverse effect on the reaction time of the addition of element and on the purity of the resulting acid salt of gamma (piperidyl) butyric acid (2).
  • step (b) The 2-(pyridylethyl) malonic acid ester (6) produced in step (a) is hydrolyzed and decarboxylated in an acidic aqueous solution. And ⁇ - (pyridyl) butyric acid acid salt (1).
  • the present invention it is possible to produce the acid salt of ⁇ - (piperidyl) butyric acid (2) in a relatively short time and with good productivity.
  • the bis (pyridylethyl) acetic acid acid salt (3) produced by the above steps (a) and (b) has a content of 3% by weight or less.
  • the method of adding hydrogen to the acid salt of (pyridyl) butyric acid (1) the addition of hydrogen is completed in a shorter period of time, and the amount of sulfur is extremely high.
  • the salt of ⁇ - (piperidyl) butyric acid (2) can be easily obtained. Best mode for carrying out the invention
  • R is a hydrogen atom or a phenol group.
  • phenol group a lower phenol group having 1 to 4 carbon atoms is preferable.
  • ⁇ in the formula (1) is an acid.
  • the acid include a mineral acid, for example, hydrochloric acid, sulfuric acid, etc., an organic acid, for example, p-tonolene snolephonic acid, trifluoromethane sulfonate. The acid strength is raised.
  • the acid salt of 7- (pyridyl) butyric acid (1) include 7- (pyridyl) butyric acid, for example, ⁇ - (2-pyridinole) butyric acid, ⁇ — ( 3 — pyridyl ) -butyric acid, y — (4 — pyridyl ) butyric acid, ⁇ — (5 — methylinole 2 — pyridinole) butyric acid, ⁇ — (6-methylinole 2 — Pyridyl) butyric acid, ⁇ - (4—methyl-3-pyridyl) butyric acid, ⁇ — (2—methylone-5—pyridinole) butyric acid, ⁇ — (5— ⁇ Butyric acid and mineral acids such as hydrochloric acid and sulfuric acid or ⁇ -toluenesulfonic acid, trifluoromethanone And salts with organic acids such as acid.
  • 7- (pyridyl) butyric acid
  • the acid salt of y- (pyridyl) butyric acid (1) can be produced by a conventionally known method with a force S.
  • 2- (pyridinolecinole) diester enolate malonate (6) can be hydrolyzed and decarboxylated in an acidic aqueous solution to obtain (Pyridinole) butyric acid acid salt (1) can be produced (step (b)).
  • 2- (pyridylethyl) malonic acid ester (6) converts butylpyridines (4) to malonic acid ester in the presence of a base.
  • the compound can be produced by reacting with (5) (step (a)).
  • the reaction in the step (a) is a so-called reaction of adding a so-called phenol.
  • the vinyl pyridines (4) include, for example, 2—vinyl pyridin, 3—vinyl pyridin, 4—vinyl pyridin, 5 — methyl 2 — vinyl pyridine, 6 — methyl 2 — vinyl pyridine, 4-methyl 1 3 — vinyl pyridine, 2 — Examples include methylol 5-vinyl pyridine, 5-ethyl 12-vinylin pyridine, and the like.
  • R i and R 2 in the formula (5) are the same or different alkyl groups, and are preferred. Is a lower alkyl group having 1 to 4 carbon atoms.
  • diester malonate (5) include, for example, dimethyl methyl malonate, getinole malonate, dipropynole malonate, malonate Acid j Sopropinole, dibutynole malonate, diisoptinole malonate and the like can be mentioned.
  • a known base commonly used in the addition of a microphone preferably an alcoholic metal alcohol
  • metal oxides such as lithium, sodium, calcium, methoxide, etc., etc. Kishido, Propoxide, Isoproboxide, 2-Methinole, 2-Propoxyd, 2-Methyl-2-Propoxyd, etc. It is badly.
  • the microcapsule force P can be applied in a solvent.
  • the solvent for example, phenol can be used.
  • the alcohol-containing alcohol include alcohols having 1 to 4 carbon atoms, specifically, methyl alcohol, alcohol, alcohol, and alcohol.
  • Alcohols such as L-Pinore-A-No-Re-Kor, I-South Mouth-Pin-Re-A-No-Re-Kore, and 2-Meth-No-Re-No-Re-Kole are listed. It is.
  • the solvent is usually used in an amount of 0.1 to 2 parts by weight, preferably 0.3 to 1 part by weight, per 1 part by weight of the vinylol pyridines (4). You can use the power s.
  • step (b) 2— (pyridyl / retinole) malonate diester (6) is hydrolyzed and decomposed in an acidic aqueous solution.
  • the acid salt of y- (pyridyl) butyric acid (1) can be produced.
  • the reaction solution containing 2— (pyridinolethienole) diester enolate malonate (6) obtained in step (a) can be subjected to hydrolysis and hydrolysis as it is.
  • 2-(pyridyl / ethynole) malonic acid isolated and purified from the reaction mixture obtained in step (a) by decarboxylation or decarboxylation.
  • the acid salt (1) of ⁇ _ (pyridinole) butyric acid can be produced.
  • the acidic aqueous solution examples include a mineral acid, for example, hydrochloric acid, sulfuric acid, etc., an organic acid, for example, ⁇ -toluenes-nolephonic acid, trifluoromethanol-no-retone.
  • An aqueous solution of an acid such as an acid is cited. 2 — (Pyridyl ethynole) Use an acid (acid aqueous solution) in an amount such that the mixed solution containing the malonic acid ester (6) and the acidic aqueous solution becomes acidic. This makes it possible to carry out hydrolysis and decarboxylation with high efficiency.
  • 2-(pyridylethyl) malonic acid diester which was isolated and purified from the reaction solution obtained after completion of the addition of the monomer obtained in step (a).
  • the amount of the terephthalate is equal to or greater than that of 2- (pyridinoletinol) malonic acid ester (6).
  • the reaction mixture obtained in step (a) after completion of the addition of the monomer is subjected to hydrolytic decomposition and decarboxylation as it is, the reaction mixture is added to the reaction mixture.
  • 2_ (Pyridylethyl) malonic acid ester (6) and the total amount of bases used for the addition of micelles and equivalents preferably 2 or more Use an equivalent amount of acid.
  • crystals of the ⁇ - (pyridinole) butyric acid acid salt (1) obtained in the step (b) contain bis (pyridylethyl) acetic acid acid salt (3), purify the crystals.
  • the content of bis (pyridylethyl) acetic acid salt (3) is 3 weight. It is preferable to set it to / 0 or less.
  • Crystals of V- (pyridyl) butyric acid acid salt (1) containing bis (pyridinoleethyl) acetic acid acid salt (3) are purified by recrystallization. be able to .
  • For recrystallization of the acid salt of ⁇ - ( pyridyl ) butyric acid (1) for example, water, alcohol, an aqueous solution of mineral acid, or a mixture thereof is used as a solvent. Can be used.
  • Hydrogenated ⁇ - (pyridyl) butyric acid acid salt (1) converts the pyridin ring into a piperidin ring, which is a countermeasure.
  • y- (piperidyl) butyric acid hydrochloric acid (2) can be produced.
  • Bi scan the pin re Jinoree Chinore
  • Moto ⁇ Ka ⁇ This means that high-purity ⁇ - (piperidyl) butyric acid acid salt (2) can be easily produced in a short time.
  • the acid salt of y- (pyridyl) butyric acid (1) it is possible to use a product formed from free y- (pyridyl) butyric acid and an acid. .
  • the acid salt of ⁇ -(pyridinole) butyric acid (1) "V-(pyridyl) butyric acid and an acid are mixed and hydrogenated to give ⁇ -( Piperidinole) Butyric acid acid salt (2) can be produced.
  • the catalyst used is an R h catalyst, a Pd catalyst or a Ru catalyst.
  • R h catalyst or Pd catalyst By using R h catalyst or Pd catalyst as catalyst, under more relaxed conditions, it is possible to achieve ⁇ y — (pyridyl ) Hydrogenation of the acid salt of butyric acid (1) can make the pyridin ring a piperidin ring.
  • the Rh catalyst the Pd catalyst or the Ru catalyst, for example, a catalyst in which Rh, Pd or Ru is supported on a carrier can be used.
  • the carrier for example, carbon, aluminum, or the like, preferably carbon, particularly activated carbon can be used.
  • the R h, P d, or Ru catalyst is referred to as R h, P d, or Ru, respectively, for the acid salt of ⁇ -( pyridyl ) butyric acid (1). 0.05% by weight or more (preferably from 0.055 to 0.3% by weight from an economic viewpoint). ) Hydrogenation of the butyric acid salt (1) can easily proceed. If the amount of the catalyst used is less than the above range, the addition of hydrogen becomes difficult, and the reaction tends to take a long time, and the reaction is not completed. In some cases, the yield of the target substance may be reduced.
  • Hydrogenation of 7- (pyridyl) butyric acid acid salt (1) can be carried out in a solvent.
  • a solvent use can be made of one which can dissolve the acid salt of ⁇ — (pyridyl) butyric acid (1) and does not affect the addition of hydrogen. And can be done.
  • water is preferred from the viewpoint of easy dissolution of the acid salt of y- (pyridyl) butyric acid (1) and safety and economy.
  • the amount of the solvent used is an amount capable of dissolving at least ⁇ -(pyridyl) butyric acid acid salt (1).
  • ⁇ -( Pyridyl) butyric acid acid salt (1) 1 part by weight Usually, 0.5 to: 10 parts by weight, preferably:! About 3 parts by weight. If the amount of water used is less than the above range, the reaction tends to take a long time because the hydrogen addition [1] is difficult to progress, and the reaction tends to take a long time. In some cases, the yield of the target is reduced without completion. If the amount of water used is higher than the above range, there is no particular problem.However, since the efficiency of the container deteriorates, it is better to be within the above range from the viewpoint of productivity. .
  • a Rh catalyst or a Pd catalyst is used as a catalyst, under conditions of low hydrogen pressure, for example:! Even under conditions of up to 40 kgf / cm 2, especially 1 to 30 kgf Z cm Z, the hydrogen addition Q can be efficiently performed.
  • Hydrogen addition can be carried out at a reaction temperature between room temperature and 140 ° C, preferably between 40 and 12 ° C. If the reaction temperature is lower than the above, the reaction time tends to be longer, and if the reaction is not completed, the yield of the target product is reduced. I don't like it because of the If the reaction temperature is higher than the above range, there is no problem with the yield, etc., but the reaction rate will be faster and the temperature control will be difficult, so safety will be high. It is better to be within the above range from the viewpoint of economical efficiency.
  • a 7- (pyridyl) butyric acid acid salt (1), a catalyst and a solvent are charged into a pressurized reactor equipped with a stirrer and a hydrogen inlet tube, and heated under stirring.
  • the acid salt (1) of y- (pyridinole) butyric acid is added to the hydrogen.
  • y- (piperidyl) butyric acid acid salt (2) is produced.
  • 0-(pyridinole) butyric acid In place of the acid salt (1), the free "y-(pyridyl) butyric acid and acid are charged into the reactor.
  • — (Piperidyl) butyric acid acid salt (2) can be produced, and such a form is also included in the present invention.
  • the y-(piperidyl)-butyric acid acid salt (2) produced from the hydrogenated potassium salt of the acid salt of y-(pyridyl) butyric acid (1) can be produced by a conventional method. By performing crystallization, recrystallization, etc., it is possible to easily isolate and purify from the reaction solution. For example, after the completion of hydrogenation, the reaction solution is filtered to remove the catalyst, the solvent is distilled off from the filtrate, and the obtained residue is recrystallized to obtain high purity. It is possible to isolate acid salts of y- (piperidyl) butyric acid.
  • reaction solution was cooled to room temperature, and 250 g of water and 3
  • Example 8 a solution containing the hydrochloride of y- (pyridyl) butyric acid was obtained as the hydrochloride of [-(pyridyl) butyric acid obtained above. 0 g (0.074). Other than that used, the production of ⁇ - (piperidyl) butyric acid hydrochloride was carried out in the same manner as in Example 8.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Hydrogenated Pyridines (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention a trait à un procédé de préparation de sels acides (2) d'acide η-(pipéridyl)butyrique par l'hydrogénation d'un sel acide (1) d'acide η-(pyridyl)butyrique (préparé, de préférence, en respectant les étapes (a) et (b) et avec une concentration en sels acides (3) d'acide acétique bis(pyridyléthyl) n'excédant pas 3 en pourcentage pondéral) dans un solvant en présence d'un catalyseur, qu'il s'agisse de rhodium, de palladium ou de ruthénium. Etape a: faire réagir un composé à base de vinylpyridine (4) avec un diester (5) d'acide malonique en présence d'une base afin de produire un diester (6) d'acide malonique 2-(pyridyléthyl). Etape b: hydrolyser et décarboxyler dans une solution aqueuse d'acide le diester (6) obtenu grâce aux opérations menées dans l'étape (a) afin de préparer le sel acide (1) d'acide η-(pyridyl)butyrique.
PCT/JP1997/003594 1996-10-07 1997-10-07 PROCEDE DE PREPARATION DE SELS ACIDES D'ACIDE η-(PIPERIDYL)BUTYRIQUE WO1998015531A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
JP51738598A JP4247415B2 (ja) 1996-10-07 1997-10-07 γ―（ピペリジル）酪酸の酸塩の製造方法
EP97943149A EP0882712B1 (fr) 1996-10-07 1997-10-07 Procede de preparation de sels acides d'acide gamma-(piperidyl)butyrique
US09/077,316 US6197961B1 (en) 1996-10-07 1997-10-07 Process for preparing acid salts of γ-(piperidyl)butyric acid
DE69721239T DE69721239T2 (de) 1996-10-07 1997-10-07 Verfahren zur hesrtellung von säuresalzen aus gamma(piperidyl)buttersäure
CA002239138A CA2239138C (fr) 1996-10-07 1997-10-07 Procede de preparation de sels acides d'acide .gamma.-(piperidyl)butyrique

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP28611996 1996-10-07
JP8/286119 1996-10-07

Publications (1)

Publication Number Publication Date
WO1998015531A1 true WO1998015531A1 (fr) 1998-04-16

Family

ID=17700185

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1997/003594 WO1998015531A1 (fr) 1996-10-07 1997-10-07 PROCEDE DE PREPARATION DE SELS ACIDES D'ACIDE η-(PIPERIDYL)BUTYRIQUE

Country Status (6)

Country Link
US (1) US6197961B1 (fr)
EP (1) EP0882712B1 (fr)
JP (1) JP4247415B2 (fr)
CA (1) CA2239138C (fr)
DE (1) DE69721239T2 (fr)
WO (1) WO1998015531A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS57193456A (en) * 1981-05-25 1982-11-27 Nippon Chemiphar Co Ltd Novel amidinopiperidine derivative and its preparation
EP0718287A2 (fr) * 1994-12-23 1996-06-26 Dr. Karl Thomae GmbH Dérivés de pipérazine, médicaments les contenant, leur application, et procédés pour leur préparation

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3875171A (en) * 1968-07-02 1975-04-01 Hoffmann La Roche Trans-4-piperidine acetic acids and esters and racemic cis-4-piperidine acetic acids and esters
CH513161A (de) * 1969-06-11 1971-09-30 Siegfried Ag Verfahren zur Herstellung von 4-Alkoxy-piperidinen
US4012396A (en) * 1973-05-21 1977-03-15 Hoffmann-La Roche Inc. Processes and intermediates for cis or trans 2-or 3-(1-acyl-3-vinyl-4-piperidine)acetic or propionic acid esters
US4433152A (en) 1981-05-25 1984-02-21 Nippon Chemiphar Co., Ltd. Amidinopiperidine derivatives
ATE206396T1 (de) * 1995-03-15 2001-10-15 Novartis Erfind Verwalt Gmbh Piperidenyl-2-alkyl substituierte lineare polyamine zur senkung intrazellulärer, endogener polyaminkonzentrationen wie z.b. putrescin, spermidin und spermin und ihr einfluss auf die zellvermehrung

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS57193456A (en) * 1981-05-25 1982-11-27 Nippon Chemiphar Co Ltd Novel amidinopiperidine derivative and its preparation
EP0718287A2 (fr) * 1994-12-23 1996-06-26 Dr. Karl Thomae GmbH Dérivés de pipérazine, médicaments les contenant, leur application, et procédés pour leur préparation

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, Vol. 58, No. 9, 29 April 1963, MIKHLINA E.E. et al., "Synthesis of 1-Azabicyclo(3.2.2)Nonane-2-Carboxylic Acid"; & ZH. OBSHCH. KHIM., 1962, Vol. 32, p. 2177-2184. *
See also references of EP0882712A4 *

Also Published As

Publication number Publication date
CA2239138C (fr) 2006-11-28
DE69721239D1 (de) 2003-05-28
EP0882712A4 (fr) 1999-12-08
EP0882712B1 (fr) 2003-04-23
EP0882712A1 (fr) 1998-12-09
DE69721239T2 (de) 2004-01-29
CA2239138A1 (fr) 1998-04-16
US6197961B1 (en) 2001-03-06
JP4247415B2 (ja) 2009-04-02

Similar Documents

Publication Publication Date Title
US20220315532A1 (en) Methods for preparing cdk4/6 inhibitor and salt and intermediate thereof
EP1939178B1 (fr) Procédé de production de la 1-benzyl-4-[(5,6-diméthoxy-1indanon)-2-yl]méthylpipéridine ou de son chlorhydrate
IL178766A (en) Processes for the formation of 1 - benzyl - 4 - [(5, 6 - dimethoxy - 1 - indanone) - 2 - il] methylphipridine and its hydrochloride
JP2012025705A (ja) （ｓ）−４−〔（４−クロロフェニル）（２−ピリジル）メトキシ〕ピペリジンのジアステレオマー塩の製造方法
JP4568398B2 (ja) ヘキサヒドロイソインドリン・酸付加塩およびその使用方法
EP1041080B1 (fr) Procédé de fabrication de pentaacétyl-beta-D-glucopyranose
WO1998015531A1 (fr) PROCEDE DE PREPARATION DE SELS ACIDES D'ACIDE η-(PIPERIDYL)BUTYRIQUE
JP2001226323A (ja) 安息香酸ベンジルの回収方法
CN101321729A (zh) 制备1-苄基-4-[(5,6-二甲氧基-1-二氢茚酮)-2-亚基]甲基哌啶的方法
CN101263117B (zh) 制备1-苄基-4-[(5,6-二甲氧基-1-二氢茚酮)-2-基]甲基哌啶或其盐酸盐的方法
JP4397990B2 (ja) ３−アルキルフラバノノール誘導体の精製法
JPS6151572B2 (fr)
US6403843B1 (en) Process for the preparation of 1-(3,4-dimethoxyphenyl)ethanol
EP1236716B1 (fr) Procede pour la fabrication de derives de 3-aminopyrrolidine-2,5-dione et de 3-aminopyrrolidine optiquement actifs
WO2005076749A2 (fr) Nouveau procede de preparation de 1-benzyl-4-[(5,6-dimethoxy-1-indanon-2-yl)methyl]piperidine
WO2008072773A1 (fr) Procédé destiné à produire (1r,2r)-2-amino-1-cyclopentanol
JP2007223964A (ja) ４−（ｎ−エチル−ｎ−イソプロピルアミノ）アニリンの精製方法
JPH01121268A (ja) ３，５−ジクロロピリジンの製造法
JPS624266A (ja) 新規４−ピリジル−４−シアノピメリン酸エステルおよびその製造法
WO1996034000A1 (fr) Procede de production de complexes de platine (ii)
JP2003206253A (ja) アルコキシ置換２−テトラロンの製造法
JPH1149722A (ja) ビフェニル誘導体の製造法
JPH02212469A (ja) Ｎ―ベンジルピロリジン誘導体又はその塩の製造方法
JPH04243867A (ja) ２−クロル−４−ピリジンメタノールの製造方法
JPH11116527A (ja) ２置換−１，３−インダンジオン誘導体の製造方法

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): CA JP US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE

ENP Entry into the national phase

Ref document number: 2239138

Country of ref document: CA

Ref country code: CA

Ref document number: 2239138

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: 09077316

Country of ref document: US

WWE Wipo information: entry into national phase

Ref document number: 1997943149

Country of ref document: EP

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWP Wipo information: published in national office

Ref document number: 1997943149

Country of ref document: EP

WWG Wipo information: grant in national office

Ref document number: 1997943149

Country of ref document: EP

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载